Factors which increase the risk for skeletal fluorosis

F.A.N. | May 2012 | By Michael Connett

The risk for developing skeletal fluorosis, and the course the disease will take, is not solely dependent on the dose of fluoride ingested. Indeed, people exposed to similar doses of fluoride may experience markedly different effects. While the wide range in individual response to fluoride is not yet fully understood, the following are some of the factors that are believed to play a role:

Impaired kidney function

Polydipsia (Excessive thirst)

Dietary deficiencies

Genetics

Acidosis (gastric acidity, rental tubular acidosis, etc)

Repetitive physical stress

Age

Pregnancy/lactation.

Impaired Kidney Function:

“[A] fairly substantial body of research indicates that patients with chronic renal insufficiency are at an increased risk of chronic fluoride toxicity. Patients with reduced glomerular filtration rates have a decreased ability to excrete fluoride in the urine. These patients may develop skeletal fluorosis even at 1 ppm fluoride in the drinking water.”
SOURCE: Schiffl H. (2008). Fluoridation of drinking water and chronic kidney disease: absence of evidence is not evidence of absence. Nephrology Dialysis Transplantation 23:411. [See commentary]

“Individuals with kidney disease have decreased ability to excrete fluoride in urine and are at risk of developing fluorosis even at normal recommended limit of 0.7 to 1.2 mg/l.”
SOURCE: Bansal R, Tiwari SC. (2006). Back pain in chronic renal failure. Nephrology Dialysis Transplantation 21:2331-2332.

“Persons with renal failure can have a four fold increase in skeletal fluoride content, are at more risk of spontaneous bone fractures, and akin to skeletal fluorosis even at 1.0 ppm fluoride in drinking water.”
SOURCE: Ayoob S, Gupta AK. (2006). Fluoride in Drinking Water: A Review on the Status and Stress Effects. Critical Reviews in Environmental Science and Technology 36:433–487.

“Though fluorosis is prevalent in certain geographic parts of the world, it is likely to occur in other parts… in people with latent kidney disease even when they consume relatively lower amounts of fluoride than in endemic regions.”
SOURCE: Reddy DR, et al. (1993). Neuro-radiology of skeletal fluorosis. Annals of the Academy of Medicine, Singapore 22(3 Suppl):493-500.

“It would not be surprising if there were some undetected cases of skeletal fluorosis in the Australian population in individuals with pathological thirst disorders and/or impaired renal function. However, the matter has not been systematically examined. This matter should be the subject of careful and systematic review.”
SOURCE: National Health and Medical Research Council. (1991). The effectiveness of water fluoridation. Canberra, Australia: Australian Government Publishing Service.

“Persons with chronic renal failures constitute a possible group at-risk with respect to the occurrence of skeletal fluorosis, because of an increased fluoride retention after oral intake. Based on the results of one study, in which the difference in retention between nephritic patients and healthy persons was quantified (average retention: 65% and 20%, respectively), a total daily intake of about 1.5 mg appears to be the maximum acceptable intake for nephritic patients. In view of the limitations of this comparative study and of the individual differences in retention and sensitivity, this figure must only be regarded as an indication.”
SOURCE: National Institute for Public Health and Environmental Protection. (1989). Integrated criteria document fluorides. Report No 758474010. The Netherlands.

“The skeletal complication of fluoride is more common in renal disease. Because of the impairment in renal excretion of fluoride, high circulating concentrations of fluoride may be achieved in renal disease.”
SOURCE: Pak CY. (1989). Fluoride and osteoporosis. Proceedings of the Society for Experimental Biology and Medicine 191: 278-86.

“A fairly substantial body of research indicates that people with kidney dysfunction are at increased risk of developing some degree of skeletal fluorosis. … However, there has been no systematic survey of people with impaired kidney function to determine how many actually suffer a degree of skeletal fluorosis that is clearly detrimental to their health.”
SOURCE: Hileman B. (1988). Fluoridation of water.Questions about health risks and benefits remain after more than 40 years. Chemical and Engineering News August 1, 1988, 26-42.

“Fluoridation of drinking water up to 1.2 ppm apparently does not pose a potential risk to bone provided the renal function is normal… We should, however, recognize that it is difficult to give a strict value for a safe fluoride concentration in drinking water, because individual susceptibility to fluoride varies.”
SOURCE: Arnala I, et al. (1985). Effects of fluoride on bone in Finland. Histomorphometry of cadaver bone from low and high fluoride areas. Acta Orthopaedica Scandinavica 56(2):161-6.

“The finding of adverse effects in (kidney) patients drinking water with 2 ppm of fluoride suggests that a few similar cases may be found in patients imbibing 1 ppm, especially if large volumes are consumed, or in heavy tea drinkers and if fluoride is indeed the cause.”
SOURCE: Johnson W, et al. (1979). Fluoridation and bone disease in renal patients. In: E Johansen, DR Taves, TO Olsen, Eds. Continuing Evaluation of the Use of Fluorides. AAAS Selected Symposium. Westview Press, Boulder, Colorado. pp. 275-293.

“In the human body, the kidneys are probably the most crucial organ during the course of low-dose long-term exposure to fluoride. Healthy kidneys excrete 50 to 60% of the ingested dose (Marier and Rose 1971). Kidney malfunction can impede this excretion, thereby causing an increased deposition of fluoride into bone. Marier (1977) has reviewed data showing that, in persons with advanced bilateral pyelonephritis, the skeletal fluoride content can be 4-fold that of similarly-exposed persons with normal kidneys. Similarly, Mernagh et al. (1977) have reported a 4-fold higher skeletal fluoride content in persons with the renal failure of osteodystrophy. It has also been shown (Seidenberg et al. 1976; Hanhijarvi 1975) that plasma F- levels can be 3 1/2 to 5 times higher than normal in persons with renal insufficiency. It is thus apparent that persons afflicted with some types of kidney malfunction constitute another group that is more “at risk” than is the general population.”
SOURCE: Marier J, Rose D. (1977). Environmental Fluoride. National Research Council of Canada. Associate Committe on Scientific Criteria for Environmental Quality. NRCC No. 16081.

“It seems probable that some people with severe or long-term renal disease, which might not be advanced enough to require hemodialysis, can still experience reduced fluoride excretion to an extent that can lead to fluorosis, or aggravate skeletal complications associated with kidney disease… It has been estimated that one in every 25 Americans may have some form of kidney disease; it would seem imperative that the magnitude of risk to such a large sub-segment of the population be determined through extensive and careful study. To date, however, no studies of this sort have been carried out, and none is planned.”
SOURCE: Groth, E. (1973). Two Issues of Science and Public Policy: Air Pollution Control in the San Francisco Bay Area, and Fluoridation of Community Water Supplies. Ph.D. Dissertation, Department of Biological Sciences, Stanford University, May 1973.

“It is generally agreed that water fluoridation is safe for persons with normal kidneys. Systemic fluorosis in patients with diminished renal function, however, seems a reasonable possibility. In such patients, fluoride may be retained with resulting higher tissue fluoride levels than in persons with normal renal function.”
SOURCE: Juncos LI, Donadio JV. (1972). Renal failure and fluorosis. Journal of the American Medical Association 222:783-5.

“Prolonged polydipsia (excessive thirst) may be hazardous to persons who live in areas where the levels of fluoride in drinking water are not those usually associated with significant fluorosis.”
SOURCE: Sauerbrunn BJ, et al. (1965). Chronic fluoride intoxication with fluorotic radiculomyelopathy. Annals of Internal Medicine 63: 1074-1078.

“All patients with dental fluorosis and anemia and/or signs of renal impairment should have radiographic examinations of the skeletal system to rule out the existence of fluoride osteosclerosis… It is likely that the reason our patient retained fluorine in his bones was that he had renal damage of long standing; without this the osteosclerosis might not have developed.”
SOURCE: Linsman JF, McMurray CA. (1943). Fluoride osteosclerosis from drinking water. Radiology 40: 474-484.

Polydipsia (Excessive thirst):

“We tried to relate the patient’s past history to his advanced fluorosis and found no evidence to suggest self-medication, industrial exposure, or dietary idiosyncrisy. Drinking water seems to have been his only source of fluoride intake. He appears to have been drinking, for 43 years, water with concentrations of fluoride from 2.4 ppm to 3.5 ppm. In the United States, these levels of fluoride have not been thought to result in clinically detectable fluorosis except for mottled teeth. This relationship appears to be that for individuals with normal water consumption. However, the risk and degree of fluorosis may also depend on the quantity of water consumed. This corrollary is suggested by the findings in our patient who developed severe crippling fluorosis while his brother, who drank the same water, showed only mottling of teeth. The brothers were exposed to identical fluoride concentration in their drinking water for the same period of time, had the same diet, lived under similar environmental circumstances, but differed by the excessive water intake by our patient. . . . Thus it appears that the probable cause for fluoride intoxication in our patient was prolonged polydipsia.”
SOURCE: Sauerbrunn BJ, et al. (1965). Chronic fluoride intoxication with fluorotic radiculomyelopathy. Annals of Internal Medicine 63: 1074-78.

“It was also evident that the osteopenic radiological picture [of fluorosis] is more commonly found in the poorer and undernourished population of the village.”
SOURCE: Mithal A, et al. (1993). Radiological spectrum of endemic fluorosis: relationship with calcium intake. Skeletal Radiology 22: 257-61.

“Diets high in fat have been reported to increase deposition of fluoride in bone and, thus, to enhance toxicity.”
SOURCE: Department of Health & Human Services. (U.S. DHHS) (1991). Review of Fluoride: Benefits and Risks. Report of the Ad Hoc Committee on Fluoride, Committee to Coordinate Environmental Health and Related Programs. Department of Health and Human Services, USA.

“Community based studies strongly suggest that calcium status modifies the type of bone changes seen in fluorosis.”
SOURCE: Krishnamachari KA. (1986). Skeletal fluorosis in humans: a review of recent progress in the understanding of the disease. Progress in Food and Nutrition Sciences 10(3-4):279-314.

“Over 90% of the persons affected with severe skeletal fluorosis, bone disease and deformities belong to the low socio-economic group of the farming community and they had generalized nutritional deficiencies.”
SOURCE: Teotia SPS, et al. (1984). Environmental fluoride and metabolic bone disease: an epidemiological study (fluoride and nutrient interactions). Fluoride 17: 14-22.

“The occurrence of this syndrome among the poorer segments of the populations is suggestive of a detrimental role of undernutrition on fluoride-induced toxicity.”
SOURCE: Krishnamachari KA, Krishnaswamy K. (1973). Genu valgum and osteoporosis in an area of endemic fluorosis. The Lancet 2: 877-879.

“Evidence of malnutrition in fluorosis-prone subjects has been cited by several investigators. Therefore, it is reasonable to suggest that subjects suffering from dietary deficiencies or metabolic malfunction may have an increased susceptibility to fluorosis.”
SOURCE: Marier JR, et al. (1963). Accumulation of skeletal fluoride and its implications. Archives of Environmental Health 664-671.

“there seemed to be a definite connection between the development of joint symptoms and poverty or intercurrent infections, since the disease appeared to be much more severe in those who had the least opportunity for healthy living.”
SOURCE: Kilborn LG, et al. (1950). Fluorosis with report of an advanced case. Canadian Medical Association Journal 62: 135-141.

“The incidence and severity of the disease had a definite relation to the economic and nutritional status of the communities… A pronounced deficiency of the vitamin C factor in the diet was especially associated with a severe incidence of the disease.”
SOURCE: Pandit CG, et al. (1940). Endemic fluorosis in South India. Indian Journal of Medical Research 28: 533-558.

“A diet rich in Ca, P, and vitamin D has an influence on the course of the intoxication, but does not prevent its occurrence.”
SOURCE: Roholm K. (1937). Fluoride intoxication: a clinical-hygienic study with a review of the literature and some experimental investigations. London: H.K. Lewis Ltd.

“In a region where there is a possibility of ingesting fluorine in toxic quantities, there will be individuals who ingest it without giving clinical symptoms of intoxication. Cristiani has applied the term latent fluorine intoxication to this condition. The manifest intoxication symptoms then develop if the fluorine intake is raised or the sensibility to fluorine increases for some reason (Ca or vitamin deficiency, etc). This explains why bones and teeth sometimes contain the same quantity of fluorine in apparently healthy individuals as in individuals with definite symptoms of intoxication.”
SOURCE: Roholm K. (1937). Fluoride intoxication: a clinical-hygienic study with a review of the literature and some experimental investigations. London: H.K. Lewis Ltd.

Genetics:

“Fluoride incorporation into bone depends on many factors, including ingestion from sources in addition to water, age, duration of residency, renal function and other disease states, remodeling rate, and genetic susceptibility. About 40% of the population in areas with water supplies naturally fluoridated at very high levels are unaffected by skeletal fluorosis, and about a third of patients who receive fluoride as a therapy for osteoporosis are described as ‘nonresponders,’ indicating that intrinsic susceptibility to fluoride varies with the individual. A genetic basis for these differences is supported by research with different strains of mice. In a large, diverse urban center like Toronto, therefore, one would expect that the population would display a range of genetic susceptibilities to fluoride…”
SOURCE: Chachra D, et al. (2010). The long-term effects of water fluoridation on the human skeleton. Journal of Dental Research 89:1219-1223.

“The results suggest that genetic factors may contribute to the variation in bone response to fluoride exposure…. The genetic influence on the efficacy and adverse effects has been demonstrated for some medications but has never been demonstrated for bone response to fluoride. The demonstration of such genetic influence on bone response to fluoride has important clinical significance. It stresses the importance to taking into account the genetic background of each individual.”
SOURCE: Mousny M, et al. (2006). The genetic influence on bone susceptibility to fluoride. Bone Aug 18; [Epub ahead of print]

“Previous studies in mice and humans, as well as epidemiological studies, have demonstrated that severity of dental fluorosis cannot be explained simply by the amount of fluoride in the tooth structure, indicating that genetics (susceptiblity to fluoride) plays an important role in dental fluorosis severity. Based on that, one can infer that in individuals ingesting the same amount of fluoride, the DF severity will be related to and/or based on individual susceptibility to fluoride (genetics).”
SOURCE: Vieira AP, Hanocock R, Eggertsson H, Everett ET, Grynpas MD. 2005. Tooth quality in dental fluorosis – genetic and environmental factors. Calcified Tissue International 76(1):17-25. January. [ Abstract ]

“The phenotype frequency distributions of several classical blood genetic markers and dermatoglyphic characters were analyzed in workers of Siberian aluminum plants who had occupational fluorosis. Comparison with healthy workers revealed significant differences in frequencies of several (genetic) markers… As we have previously shown, risk of occuapational fluorosis in Siberian workers employed in aluminum industry is associated wtih several erthrocytic isoantigens and a set of particular qualitative dermatoglyphic characters.”
SOURCE: Lavryashina MB, et al. (2003). A study of the genetic basis of susceptibility to occupational fluorosis in aluminum industry workers of Siberia. Russian Journal of Genetics 39: 823-827.

“This study helped 1) to establish the existence of genetic predisposition to fluorosis and develop criteria for estimating it, and 2) to prove that predisposition to fluorosis was associated wtih the same dermatoglyphic features in the workers of both industrial groups.”
SOURCE: Polzik EV, et al. (1994). A method for estimating individual predisposition to occupational fluorosis. Fluoride 27: 194-200.

“We suggest that predisposition to fluorosis (chronic toxicity) is biochemically mediated and genetically determined. This would explain the marked variation in fluorosis prevalence in areas with comparable levels of fluoride intake and the selectivity of the disease within the same area. Further studies are necessary to elucidate the complex interaction between calcium, iodine, sex hormones, vitamins and fluoride ions.”
SOURCE: Anand JK, Roberts JT. (1990). Chronic fluorine poisoning in man: a review of literature in English (1946-1989) and indications for research. Biomedicine & Pharmacotherapy 44: 417-420.

Gastric Acidity:

“The absorption rate of fluoride from the stomach is dependent on the pH of the gastric contents and chronic metabolic acidosis induces reduction in the renal clearance of fluoride. This again can result in major disturbances in enamel with mineralization defects resembling fluorosis due to high concentrations of fluoride in bone and enamel associated with the acidotic state. The use of fluoride supplements is therefore contraindicated in RTA associated enamel hypoplasia.”
SOURCE: Krishnan B, et al. (2012). Distal renal tubular acidosis: An uncommon cause of enamel hypoplasia in siblings. International Journal of Stomatology & Occlusion Medicine 10.1007/s12548-012-0061-8.

“The excretion of absorbed fluoride occurs almost exclusively via the kidneys, a process which is directly related to urinary pH. Thus, fluoride balance and tissue concentrations and the risk of [dental] fluorosis are increased by factors such as high protein diets, residence at high altitude, and certain metabolic and respiratory disorders that decrease pH. Factors that increase urinary pH and decrease the balance of fluoride include vegetarian diets, certain drugs and some other medical conditions.”
SOURCE: Whitford GM. (1997). Determinants and mechanisms of enamel fluorosis. Ciba Found Symp. 205:226-41.

“We studied the relationship of gastric acid in 150 aluminum workers to the degree of severity of fluorosis. The gastric acid was determined by the Acido-test. Figure 13 shows a distinct correlation namely, with increasing severity of fluorosis the percentage of hyperacid persons increases and the proportion of hypo- or an-acid persons decreases. The differences were statistically significant. These findings prove that fluoride resorption is obviously diminished by a deficiency of gastric acid and that it is enhanced by hyperacidity.”
SOURCE: Franke J, et al. (1975). Industrial fluorosis. Fluoride 8: 61-83.

Repetitive/Physical Stress:

“it appears that the development of new fluorotic bone occurs at those sites most subjected to strain and minor trauma.”
SOURCE: Littleton J. (1999). Paleopathology of skeletal fluorosis. American Journal of Physical Anthropology 109: 465-483.

“In man, the spine is the most common part of the skeleton to be first affected (with fluorosis) and also severely so because it is required to sustain the erect posture and has stresses and strains.”
Prasad VS, Reddy DR. (1994). Posttraumatic pseudomenigocoele of cervical spine in a patient with skeletal fluorosis: Case report. Paraplegia 32:627-30.

“It is notable that the symptoms and radiological changes occur first in areas of greater muscular activity… Both Siddiqui and Singh et al noted… the selective effect of this halide on the joints which are most used.”
SOURCE: Anand JK, Roberts JT. (1990). Chronic fluorine poisoning in man: a review of literature in English (1946-1989) and indications for research. Biomedicine & Pharmacotherapy 44: 417-420.

In “Indian basket weavers exposed to fluoride, it was observed that the much used left arm and wrist were particularly susceptible to fluorotic exostosis… [T]he areas suffering repeated or constant stress or trauma, and as a result requiring ongoing repair, may be areas of increased circulation and metabolism and, as a consequence, increased deposition of fluorides.”
SOURCE: Carnow BW, Conibear SA. (1981). Industrial fluorosis. Fluoride 14: 172-181.

“Radiological changes in industrial fluorosis suggest that physical strain on bones, ligaments, and joints play an important role in the development of the lesions.”
SOURCE: Boillat MA, et al. (1980). Radiological criteria of industrial fluorosis. Skeletal Radiology 5: 161-165.

“These [fluorotic] changes first appear at sites of greatest metabolic activity and stress within a given bone and in bones that are under the greatest stress from weight bearing and locomotion.”
SOURCE: Shupe JL, Olson AE. (1971). Cinical aspects of fluorosis in horses. Journal of the American Veterinary Association 158: 167-174.

“The radiographs of our case show the typical changes of severe skeletal fluorosis. Bones subjected to greatest stress are most affected (by fluorosis), probably due to their greater calcium turnover… The severe elbow involvement in our case may have been related to his occupation as a carpenter.”
SOURCE: Webb-Peploe MM, Bradley WG. (1966). Endemic fluorosis with neurological complications in a Hampshire man. Journal of Neurology, Neurosurgery and Psychiatry 29:577-583.

“The onset of fluorosis in humans is favored by physcial stress, affecting the skeletal regions most used by the individual. Continued surface abrasions of a bone with high fluoride and magnesium content may release relatively high levels of these ions at the crystal-solution interface, promoting crystallization of magnesium fluoride during replacement of damaged bone.”
SOURCE: Marier JR, et al. (1963). Accumulation of skeletal fluoride and its implications. Archives of Environmental Health 6: 664-671.

“Physical strain may also contribute, because the disease was found predominantly in manual workers, who showed involvement of cervical spine and skull – a condition rarely seen by Roholm.”
SOURCE: Singh A, et al. (1961). Skeletal fluorosis and its neurological complications. Lancet 1: 197-200.

“The degree of osteosclerosis was found to be related to the duration of intoxication and the concentration of fluorine in the water. Physical strain was also found responsible: the greater the strain, the more pronounced were the changes observed… Pain and stiffness were more severe in the joints used most by the individual – for example, the wrists, shoulders, and neck in the females, who were mostly engaged in household work: and the lumbar spine and the joints of the lower limbs in the males working in the fields.”
SOURCE: Siddiqui AH. (1955). Fluorosis in Nalgonda district, Hyderabad-Deccan. British Medical Journal ii (Dec 10): 1408-1413.

Age:

“[A]ged populations are likely to be the most vulnerable to any negative effects of municipal fluoride administration because of both fluoride accumulation in bone over time and age-related declines in the mechanical properties of bone.”
SOURCE: Chachra D, et al. (2010). The long-term effects of water fluoridation on the human skeleton. Journal of Dental Research 89:1219-1223.

“Fluoride toxicity afflicts children more severely and over a shorter period of exposure (about 6 months) as compared to adults. This is because the rapidly growing bones of children are metabolically active and more vascular and thus absorb and accumulate fluoride faster and in greater amounts than older bones, particularly at the sites of bone growth and physiological calcifications.”
SOURCE: Teotia M, Teotia SP, Singh KP. (1998). Endemic chronic fluoride toxicity and dietary calcium deficiency interaction syndromes of metabolic bone disease and deformities in India: year 2000. Indian Journal of Pediatrics 65:371-81.

“To date, animal studies of fluoride effects on bone have used young and healthy experimental animals exclusively. The effects of fluoride on old animals, that more closely represent people most likely to fracture, have not been studied…. In older rats receiving 50 ppm fluoride, failure stress was decreased by as much as 29%. Such dramatic losses in bone strength only have been shown previously in studies where fluoride intake was accompanied by calcium deficiency, yet, in this study, calcium intake in the older rats was no different from that in the younger rats… [I]t is possible that aging effects and fluoride incorporation in the bone act synergistically to decrease bone strength.”
SOURCE: Turner CH, et al. (1995). Fluoride reduces bone strength in older rats. Journal of Dental Research 74:1475-81.

“In our opinion, growing children with active bone metabolism, if exposed to high fluoride intake, are more prone to develop skeletal fluorosis than adults. As bone ages and becomes more or less stabilized in the remodelling of its Haversian systems, less fluoride may be deposited. We observed that individuals residing in an endemic area since birth develop more severe skeletal fluorosis than those who have moved into the endemic zone after 17 to 18 years of age when bone growth has created.”
SOURCE: Teotia M, Teotia SPS. (1973). Further observations on endemic fluoride-induced osteopathies in children. Fluoride 6: 143-151.

“Mottling was the result of the action of fluoride on osteoblasts during bone formation. Young bones undergoing extensive remodeling showed extensive mottling, while old bones with scant remodeling showed little mottling.”
SOURCE: Johnson LC. (1965). Histogenesis and mechanisms in the development of osteofluorosis. In: H.C.Hodge and F.A.Smith, eds : Fluorine chemistry, Vol. 4. New York, N.Y., Academic press (1965) 424-441.

“A large calcium requirement in the organism increases the sensitivity to fluorine. Bone symptoms are produced most readily in young, growing individuals.”
SOURCE: Roholm K. (1937). Fluoride intoxication: a clinical-hygienic study with a review of the literature and some experimental investigations. London: H.K. Lewis Ltd.

Pregnancy/Lactation:

“It appears that fluoride ingestion during lactation created a heightened state of calcium homeostatic stress. As a result, bone mineral was mobilized by resorption of the endosteal surface and by cavitation of the interior of the cortex.”
SOURCE: Ream LJ, et al. (1983). Fluoride ingestion during multiple pregnancies and lactations: microscopic observations on bone of the rat. Virchows Arch [Cell Pathol] 44: 35-44.

“Excessive fluoride ingestion in pregnant women may possibly poison and alter enzyme and hormonal systems in the fetus causing disturbances in osteoid formation and mineralization.”
SOURCE: Christie DP. (1980). The spectrum of radiographic bone changes in children with fluorosis. Radiology 136:85-90.

“A large calcium requirement in the organism increases the sensitivity to fluorine. Bone symptoms are produced most readily in young, growing individuals. The toxic effect on cattle becomes visible especially in conjunction with pregnancy and lactation.”
SOURCE: Roholm K. (1937). Fluoride intoxication: a clinical-hygienic study with a review of the literature and some experimental investigations. London: H.K. Lewis Ltd.